We propose to set up a Nuclear Magnetic Resonance (NMR) laboratory for the study of cellular metabolism in health and disease. The instrument requested is a high resolution NMR spectrometer with a 1.89 Tesla, 30 cm horizontal bore superconducting magnet, suitable for in vivo and in vitro studies. Although five nuclei (1H, 19F, 31P, 13C, and 23 Na) can be measured with the spectrometer, this project will focus on investigations related to bioenergetics and cellular metabolism in different organs by 31P NMR. The availability of this instrument would add a new dimension to the existing research projects outlined below: 1) studies on mechanism of hypoxic and ischemic injury (kidney, heart, lungs and liver); 2) metabolic aspect of hepatobiliary function (liver perfusion and hepatocytes); 3) biochemical aspects of myopathies; and 4) metabolism of tumor and leukemic cells. Different species of animals (rats, rabbits, mice, and hamsters) will be used for in vivo NMR study of kidney, liver, skeletal muscle, and heart using a surface coil. For either isolated organ perfusion (kidney, heart or lung) or tissue preparation, a specially designed perfusion chamber with 5-turn radiofrequency coil will be used. A surface coil (2.5 cm diameter) will be used for human forearm muscle studied in vivo at rest and during exercise. A gradient coil will be incorporated for proton imaging. Studies using this instrument will permit multiple (shared) use on investigations related to bioenergetics and cellular metabolism of organs and cells in health and disease. With the eventual development and installation of total body magnets capable of proton NMR imaging and high resolution spectroscopy, studies proposed in this application should provide valuable fundamental information, applicable to clinical diagnosis and therapeutics. The non-invasive biochemical approach to the study of these problems may involve as yet undiscovered metabolic features of normal and diseased cells/organs, and as such may also enhance our understanding of fundamental biologic interactions.